The interactions of alkylaminoacridines and alkylaminoquinolines with defined sequence deoxyribonucleotides and with S. typhimurium and V79 cell DNA in vivo will be investigated to determine the mechanism of mutation induction by these compounds. Three hypotheses will be tested: (1) There is a correlation between the amount of drug bound to DNA, the base pair distribution of the drug and the number of frameshift revertants in S. typhimurium; (2) The number of frameshift revertants caused by the drugs is a function of its ability to stabilize mispaired or looped-out polynucleotide complexes; (3) The number of frameshift revertants is related to the length of the side chain, the chirality of the side chain, and the number of fused aromatic rings. These hypotheses will be tested using drugs with chiral side chains and the photo-affinity labeling technique. In addition, the structures of the drug - DNA adducts formed upon photolysis will be elucidated. This study seeks to develop a knowledge of the mode of action of mutagenic drugs which do not require metabolic activation. This knowledge is important in its own right and in addition can be used to design new drugs with high efficacy but reduced mutagenicity. This study is also unique in that it addresses the effect of chirality, length of the side chain, and the number of fused aromatic rings on mutagenicity and also addresses the chemistry of nitrene addition to DNA.